Disentangling the puzzle of ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by problems in paying attention[1] (the incapacity of attending with a necessary degree of constancy to any object), hyperkinetic activity (remarkable motor activity which appears urgent) and a lack of controlled behavior (unstable mood, fits of rage, tendency to aggressively or excitability) that interferes with functioning or normal development [1,2].

This disorder was formally conceptualized as a pathological disorder at the US in 2000 (on the DSM-IV-TR[2]). Within the European clinical practice, ADHD was first diagnosed with precise metrics and clinical scales in 1993 as defined within the ICD-10 classification list. Before that, ADHD symptoms were diagnosed as hyperkinetic disorders or attention deficit disorder (ADD) although its treatment through medication and the consideration of ADHD as a psychiatric disorder only became significant in the 1970s [6].

‘When any object of external sense, or of thought, occupies the mind in such a degree that a person does not receive a clear perception from any other one, he is said to attend to it’

Alexander Crichton, 1798

Current clinical diagnostic criteria involve a qualitative evaluation of impaired attention levels, hyperactivity and lack of controlled behavior (involving deshinibition, recklessness or impulsivity) based on the criteria described in DSM/ICD medical classifications list. As the two guidelines are slightly different, the prevalence of the disease will vary according to which criterion is applied. In particular, DSM-IV criteria diagnoses 5-7% of children [4], while ICD-10 shows a 1-2% diagnose rate in children [5].

Additionally, as both hyperactivity and inattention also arise as a symptom of anxiety or depressive disorders in children [9], both clinical diagnose guides require that ADHD is only diagnosed when the symptoms are not better explained by any other disorder. As to increase specificity of the diagnose and phenotype that ADHD describes, three subtypes of ADHD are described in both clinical manual for diagnosis (DSM and ICT):

  • ADHD-I: predominantly inattentive type
  • ADHD-H: predominantly hyperactive/impulsive subtype
  • ADHD-C: combined type

However, the clinical classification of ADHD still lacks a neurophysiological counterpart, and in fact, different ADHD subtypes have been proposed based on electrophysiological signals (see [11] or [12] for more details).

With this complexity in mind, current qualitative evaluation of ADHD results in a diagnostic accuracy of 61% [13]. Such accuracy has been recently improved by clinical decision support systems (DSS) that involve the analysis of resting-state EEG to the 88% (see [13], the TBR test), although it’s clinical relevance in separating different subtypes remains under discussion.

Despite the complications in diagnosis, ADHD is described as a disorder that impairs the appropriate development and functioning of the patient. For this reason, it’s early and an accurate diagnose of ADHD becomes crucial as to treat and ensure an appropriate development and functioning of the patient.

In terms of treatment, current therapies for ADHD are varied and involve combination of counseling, medication and lifestyle changes [2]. Medications for ADHD are mostly based on stimulants (i.e amphetamine, methylphenidate, etc) that block the dopamine and nor-adrenaline pathways, drugs that in normal children/adults is reported to enhance focal attention and general performance-enhancement [6]. Note however that, to this date, there is no knowledge on which medication improves symptoms with lower side effects and they are currently applied as ‘trial and error’ for each diagnosed children [7]. Additionally, a recent longitudinal study report that stimulant medication; behavior therapy or multimodal treatments in ADHD have limited long-term beneficial effects [8].

This overall situation opens the question of whether further understanding of the neurological aspects of the disease is needed, opening the door to the development of quantifiable biologically-driven markers of ADHD.

  1. Cormier E. Attention Deficit/Hyperactivity Disorder: A Review and Update. J Pediatr Nurs. 2008;23: 345–357. doi:10.1016/j.pedn.2008.01.003
  2. Attention Deficit Hyperactivity Disorder. Natl Inst Ment Heal. 2016;
  3. FORD T, GOODMAN R, MELTZER H. The British Child and Adolescent Mental Health Survey 1999: The Prevalence of DSM-IV Disorders. J Am Acad Child Adolesc Psychiatry. Elsevier; 2003;42: 1203–1211. doi:10.1097/00004583-200310000-00011
  4. Willcutt EG. The Prevalence of DSM-IV Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review. Neurotherapeutics. 2012;9: 490–499. doi:10.1007/s13311-012-0135-8
  5. Cowen P, Harrison P, Burns T. Shorter Oxford textbook of psychiatry. Oxford University Press; 2012.
  6. Lange KW, Reichl S, Lange KM, Tucha L, Tucha O. The history of attention deficit hyperactivity disorder. ADHD Atten Deficit Hyperact Disord. 2010;2: 241–255. doi:10.1007/s12402-010-0045-8
  7. McDonagh M, Peterson K, Thakurta S, Low A. Pharmacologic Treatments for Attention Deficit Hyperactivity Disorder. Oregon Heal Sci Univ. 2011; Available: https://www.ncbi.nlm.nih.gov/books/NBK84419/pdf/Bookshelf_NBK84419.pdf
  8. Molina BSG, Hinshaw SP, Swanson JM, Arnold LE, Vitiello B, Jensen PS, et al. The MTA at 8 Years: Prospective Follow-up of Children Treated for Combined-Type ADHD in a Multisite Study. J Am Acad Child Adolesc Psychiatry. 2009;48: 484–500. doi:10.1097/CHI.0b013e31819c23d0
  9. WHO. The ICD-10 Classification of Mental and Behavioural Disorders. IACAPAP E-textb child Adolesc Ment Heal. 2013;55: 135–139. doi:10.4103/0019
  10. Clarke AR, Barry RJ, Dupuy FE, Heckel LD, McCarthy R, Selikowitz M, et al. Behavioural differences between EEG-defined subgroups of children with Attention-Deficit/Hyperactivity Disorder. Clin Neurophysiol. International Federation of Clinical Neurophysiology; 2011;122: 1333–1341. doi:10.1016/j.clinph.2010.12.038
  11. Ogrim G, Kropotov J, Hestad K. The quantitative EEG theta/beta ratio in attention deficit/hyperactivity disorder and normal controls: Sensitivity, specificity, and behavioral correlates. Psychiatry Res. Elsevier Ltd; 2012;198: 482–488. doi:10.1016/j.psychres.2011.12.041
  12. Arns M, Gunkelman J, Breteler M, Spronk D. EEG phenotypes predict treatment outcome to stimulants in children with ADHD. J Integr Neurosci. 2008;7: 421–438. doi:10.1142/S0219635208001897
  13. Snyder SM, Rugino TA, Hornig M, Stein MA. Integration of an EEG biomarker with a clinician’s ADHD evaluation. Brain Behav. 2015;5: 1–17. doi:10.1002/brb3.330
  14. NEBA HEALTH L. De novo classification Request for Neuropsychiatric EEG-based assessment AID for ADHD (NEBA) system. FDA. 2011;

[1] According to [6], altered behavior in ADHD is clearly represented in ‘The story of fidgety Phillip’, drawn by the famous psychiatrist Heinrich Hoffman.

[2] DSM is the acronym for the Diagnostic and Statistical Manual of Mental Disorders, a manual published by the American Psychiatric Association to offer standardized criteria for the classification of mental disorders used worldwide. The EU equivalent is the ICD- International Statistical Classification of Diseases and Related Health Problems as published by the WHO.

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